Genetic variation between individuals is due in large part to the common occurrence of single nucleotide polymorphisms (SNPs). These genetic variations are also likely to be involved in numerous complex diseases. It is proposed to develop a fully automated mass spectrometric assay for SNP analysis. A novel cleavable primer will be used in an extension reaction; this approach is advantageous for facile multiplexing and purification of the short resultant oligonucleotides. Measurement times are less than five seconds per (multiplexed) sample, with standard deviations in mass measurement of the added base of less than two Daltons. R and D work will center on increasing the ease and robustness of multiplex primer-probe design, multiplex SNP data analysis, validation studies, and automation development. PROPOSED COMMERCIAL APPLICATION The high frequency of single nucleotide polymorphisms (SNPs) in the human genome makes them a valuable source of genetic markers for identity testing, genome mapping, risk assessment, and medical diagnostics. Assays for SNPs have potential commercial applications in the pharmaceutical industry for the prevention, diagnosis and treatment of diseases where the susceptibility of individuals and the outcome of treatment is related to particular genetic polymorphisms. Because it is likely that many genetic loci from hundred to thousands of individuals will need to be screened in order to assess the significance of specific genetic variants, the high-throughput capabilities of the assay will be especially important.